Cerebral glucose metabolism has been studied using position emission tomography (PET) under euglycemic clamp conditions in Pima Indians with normal, impaired glucose tolerance, and noninsulin- dependent diabetes mellitus (NIDDM). Each volunteer has undergone 2 studies, one during euglycemia (glucose 100 mg per dl and euinsulinemia), and one under euglycemia and hyperinsulinemia (plasma insulin approximately 1000 mu U/ml). In each study the glucose clamp is maintained for a half hour prior to the start of the PET scan which is indicated by intravenous injection of fluorodeoxyglucose (FDG). The PET data is accumulated for 2 hours, during which the euglycemic glucose clamp is maintained. Static PET images obtained 45 minutes after injection of fluorodeoxyglucose have been analyzed and the local rates of glucose utilization in 201 regions of the central nervous system determined. Preliminary evaluation of the data obtained during the 2 clamp studies indicate a marked decrease in cerebral accumulation of FDG during hyperinsulinemia. This appears to be due to increased peripheral glucose uptake rather than due to depression of cerebral glucose metabolism. No specific area of altered glucose metabolism during hyperinsulinemia vs. euinsulinemia has been identified although scattered areas have shown significant alterations using uncorrected student T tests. The number of patients studied to-date is too small to allow firm conclusions to be reached regarding the effects of insulin on cerebral glucose utilization or to allow comparison of normal vs. diabetic Pimas and Pima vs. Caucasian controls.